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Ref Type Journal Article
PMID (32955570)
Authors Inoue Y, Yoshimura K, Nishimoto K, Inui N, Karayama M, Yasui H, Hozumi H, Suzuki Y, Furuhashi K, Fujisawa T, Enomoto N, Nakamura Y, Asada K, Uto T, Fujii M, Matsui T, Matsuura S, Hashimoto D, Toyoshima M, Kusagaya H, Matsuda H, Inami N, Kaida Y, Niwa M, Ito Y, Sugimura H, Suda T
Title Evaluation of Programmed Death Ligand 1 (PD-L1) Gene Amplification and Response to Nivolumab Monotherapy in Non-small Cell Lung Cancer.
Journal Vol Issue Date Pages Journal Short Title
JAMA network open 3 9 2020 Sep 01 e2011818 JAMA Netw Open
URL
Abstract Text Robust predictors for response to anti-programmed death 1 and its ligand (PD-1/PD-L1) immunotherapy in non-small cell lung cancer (NSCLC) are not fully characterized.To evaluate whether PD-L1 (CD274) copy number gains (CNGs), comprising amplification and polysomy, in pretreatment specimens assessed by fluorescence in situ hybridization are associated with response to nivolumab monotherapy in NSCLC.This multicenter cohort study enrolled 200 patients, of whom 194 had assessable tumors, with advanced or recurrent NSCLC who were treated with nivolumab after progression following prior treatment at 14 institutions in Japan between July 2016 and December 2018. Median (interquartile range) duration of follow-up was 12.6 (5.6-20.4) months. Data were analyzed from December 2019 to February 2020.Sequential nivolumab was given on day 1 of a 14-day cycle. Response was assessed every 4 cycles using Response Evaluation Criteria in Solid Tumors version 1.1.Overall response rate (ORR) according to the PD-L1 copy number status. Additional end points were progression-free survival, overall survival, and PD-L1 tumor proportion score (TPS) assessed by immunohistochemistry based on PD-L1 copy number status.A total of 6 of the 200 patients were excluded because of poor-quality tumor specimens for the biomarker study, resulting in 194 assessable patients. Of these, 155 (79.9%) were men, with a median (range) age of 69 (43-83) years. PD-L1 CNGs were identified in 32 patients (16.5%), including 5 (2.6%) with amplification and 27 (13.9%) with polysomy. The ORR among patients with and without PD-L1 CNGs was 28.1% (95% CI, 13.7%-46.7%) and 17.9% (95% CI, 12.3%-24.7%), respectively. Although patients with PD-L1 polysomy did not demonstrate improved ORR (18.5% [95% CI, 6.3%-38.1%]) compared with those without PD-L1 CNGs, 4 of 5 patients (80.0% [95% CI, 28.4%-99.5%]) with PD-L1 amplification showed response, among whom median duration of response was not reached. Patients with PD-L1 amplification showed excellent survival outcomes for progression-free and overall survival. Overall, 3 PD-L1-amplified tumors (60.0%) showed PD-L1 TPS of at least 80%, but 2 (40.0%) had PD-L1 TPS of 15% or less.In this study, tumor PD-L1 amplification but not polysomy was associated with response to nivolumab monotherapy among patients with NSCLC. External validation with a larger sample size is warranted.

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Molecular Profile Treatment Approach
Gene Name Source Synonyms Protein Domains Gene Description Gene Role
Therapy Name Drugs Efficacy Evidence Clinical Trials
Drug Name Trade Name Synonyms Drug Classes Drug Description
Gene Variant Impact Protein Effect Variant Description Associated with drug Resistance
Molecular Profile Indication/Tumor Type Response Type Therapy Name Approval Status Evidence Type Efficacy Evidence References
CD274 amp lung non-small cell carcinoma predicted - sensitive Nivolumab Case Reports/Case Series Actionable In a clinical case study, a CD274 (PD-L1) amplified non-small cell lung carcinoma patient treated with Opdivo (nivolumab) achieved stable disease with a 20% reduction in tumor growth and a progression-free survival of 9.7 months (PMID: 32955570). 32955570
CD274 amp lung non-small cell carcinoma predicted - sensitive Nivolumab Clinical Study - Cohort Actionable In a clinical study, treatment with Opdivo (nivolumab) did not result in a significant overall response rate (ORR) in non-small cell lung cancer (NSCLC) patients with a CD274 copy number gain (CNG; amplification and polysomy) vs patients without a CNG (28.1% vs. 17.9%; p=0.22), but NSCLC patients with CD274 amplification demonstrated an ORR of 80% (4/5), a 1-year progression-free survival of 80%, a 1-year overall survival of 100%, and the median duration of response was not yet reached (PMID: 32955570). 32955570
CD274 over exp lung non-small cell carcinoma predicted - sensitive Nivolumab Clinical Study - Cohort Actionable In a clinical study, non-small cell lung carcinoma patients with a CD274 (PD-L1) TPS of >=50% treated with Opdivo (nivolumab) achieved an overall response rate of 45.8% vs. 15.9% (p=0.002) and a median progression-free survival of 8.1 months vs. 2.2 months (HR=0.54; 95% CI: 0.33-0.90; p=0.02), and demonstrated an overall survival benefit (HR=0.44; 95% CI: 0.23-0.84; p=0.01) compared to patients with a TPS of < 50% (PMID: 32955570). 32955570